VEGFR-2/BRAF-IN-2 (Compound 4a) is a dual VEGFR-2 and BRAF kinases inhibitor with IC50 values of 0.111, 0.089 and 0.071 µM against VEGFR-2, BRAFV600E and BRAFWT, respectively. VEGFR-2/BRAF-IN-2 induces apoptosis and arrests the cell cycle mainly in the G1 phase[1].
IC50 & Target
VEGFR2
0.111 μM (IC50)
BRafV600E
0.089 μM (IC50)
BRAFWT
0.071 μM (IC50)
分子量
608.05
Formula
C26H21ClF3N5O3S2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Hassan RA, et al. Novel antiproliferative agents bearing substituted thieno[2,3-d]pyrimidine scaffold as dual VEGFR-2 and BRAF kinases inhibitors and apoptosis inducers; design, synthesis and molecular docking. Bioorg Chem. 2022 May 10;125:105861.
VEGFR2-IN-1 is a potent and selective VEGFR2 inhibitor (IC50=19.8 nM). VEGFR2-IN-1 inhibits cell proliferation and migration through apoptosis activation and VEGFR2 inhibition[1].
IC50 & Target
VEGFR2
19.8 nM (IC50)
体外研究 (In Vitro)
VEGFR2-IN-1 (compound 17; 0.1, 1, 10, 100 μM; 48 hours) shows an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells[1]. VEGFR2-IN-1 (MCF-7 cells; 48 hours) induces cell cycle arrest at the G1 and S-phases[1]. VEGFR2-IN-1 (MCF-7 cells) shows the upregulation of pro-apoptotic genes (p53, Bax, caspases-3, caspases-9) and downregulation of antiapoptotic gene (Bcl-2)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay[1]
Cell Line:
MCF-7, MDA-MB-231, MCF-10A cells
Concentration:
0.1, 1, 10, 100 μM
Incubation Time:
48 hours
Result:
Exhibited an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells.
体内研究 (In Vivo)
VEGFR2-IN-1 (4.2 mg/kg; i.p.; once a day for 7 days) shows anticancer activity with an improvement of hematological, biochemical parameters[1]. Animal Model: Male Swiss albino mice, 21-28 g (Xenograft model)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Swiss albino mice, 21-28 g (Xenograft model)[1]
Dosage:
4.2 mg/kg
Administration:
i.p.; once a days; 7 days
Result:
Showed anticancer activity by having a tumor inhibition ratio of 54.2% with an improvement of hematological, biochemical parameters.
分子量
398.48
Formula
C22H18N6S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Nafie MS, Boraei ATA. Exploration of novel VEGFR2 tyrosine kinase inhibitors via design and synthesis of new alkylated indolyl-triazole Schiff bases for targeting breast cancer. Bioorg Chem. 2022; 122:105708.
VEGFR2-IN-1 is a potent and selective VEGFR2 inhibitor (IC50=19.8 nM). VEGFR2-IN-1 inhibits cell proliferation and migration through apoptosis activation and VEGFR2 inhibition[1].
IC50 & Target
VEGFR2
19.8 nM (IC50)
体外研究 (In Vitro)
VEGFR2-IN-1 (compound 17; 0.1, 1, 10, 100 μM; 48 hours) shows an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells[1]. VEGFR2-IN-1 (MCF-7 cells; 48 hours) induces cell cycle arrest at the G1 and S-phases[1]. VEGFR2-IN-1 (MCF-7 cells) shows the upregulation of pro-apoptotic genes (p53, Bax, caspases-3, caspases-9) and downregulation of antiapoptotic gene (Bcl-2)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay[1]
Cell Line:
MCF-7, MDA-MB-231, MCF-10A cells
Concentration:
0.1, 1, 10, 100 μM
Incubation Time:
48 hours
Result:
Exhibited an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells.
体内研究 (In Vivo)
VEGFR2-IN-1 (4.2 mg/kg; i.p.; once a day for 7 days) shows anticancer activity with an improvement of hematological, biochemical parameters[1]. Animal Model: Male Swiss albino mice, 21-28 g (Xenograft model)[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Swiss albino mice, 21-28 g (Xenograft model)[1]
Dosage:
4.2 mg/kg
Administration:
i.p.; once a days; 7 days
Result:
Showed anticancer activity by having a tumor inhibition ratio of 54.2% with an improvement of hematological, biochemical parameters.
分子量
398.48
Formula
C22H18N6S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Nafie MS, Boraei ATA. Exploration of novel VEGFR2 tyrosine kinase inhibitors via design and synthesis of new alkylated indolyl-triazole Schiff bases for targeting breast cancer. Bioorg Chem. 2022; 122:105708.
VEGFR2-IN-1 is a potent and selective VEGFR2 inhibitor (IC50=19.8 nM). VEGFR2-IN-1 inhibits cell proliferation and migration through apoptosis activation and VEGFR2 inhibition[1].
IC50 & Target
VEGFR2
19.8 nM (IC50)
体外研究 (In Vitro)
VEGFR2-IN-1 (compound 17; 0.1, 1, 10, 100 μM; 48 hours) shows an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells[1]. VEGFR2-IN-1 (MCF-7 cells; 48 hours) induces cell cycle arrest at the G1 and S-phases[1]. VEGFR2-IN-1 (MCF-7 cells) shows the upregulation of pro-apoptotic genes (p53, Bax, caspases-3, caspases-9) and downregulation of antiapoptotic gene (Bcl-2)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay[1]
Cell Line:
MCF-7, MDA-MB-231, MCF-10A cells
Concentration:
0.1, 1, 10, 100 μM
Incubation Time:
48 hours
Result:
Exhibited an effective and selective agent against MCF-7 (IC50=1.18 μM), MDA-MB-231 (IC50=10.49 μM), MCF-10A (IC50=24.76 μM) cells.
体内研究 (In Vivo)
VEGFR2-IN-1 (4.2 mg/kg; i.p.; once a day for 7 days) shows anticancer activity with an improvement of hematological, biochemical parameters[1]. Animal Model: Male Swiss albino mice, 21-28 g (Xenograft model)[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Male Swiss albino mice, 21-28 g (Xenograft model)[1]
Dosage:
4.2 mg/kg
Administration:
i.p.; once a days; 7 days
Result:
Showed anticancer activity by having a tumor inhibition ratio of 54.2% with an improvement of hematological, biochemical parameters.
分子量
398.48
Formula
C22H18N6S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Nafie MS, Boraei ATA. Exploration of novel VEGFR2 tyrosine kinase inhibitors via design and synthesis of new alkylated indolyl-triazole Schiff bases for targeting breast cancer. Bioorg Chem. 2022; 122:105708.
JK-P3 is a potent and pan VEGFR2 inhibitor, with IC50s of 7.83 μM, 27 μM and 5.18 μM for VEGFR2, FGFR1 and FGFR3, respectively. JK-P3 can inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling, also inhibits endothelial monolayer wound closure and angiogenesis, as well as fibroblast growth factor receptor kinase activity in vitro. JK-P3 has anti-angiogenic activity[1].
IC50 & Target[1]
VEGFR2
7.83 μM (IC50)
FGFR1
27 μM (IC50)
FGFR3
5.18 μM (IC50)
体外研究 (In Vitro)
JK-P3 (0.01-10 μM; 1 hour) inhibits VEGF-A-mediated VEGFR2 phosphorylation and downstream signalling[1]. JK-P3 (0.01-10 μM; 16 hours) dose not inhibit HUVEC cell proliferation at 0.01~1 μM, and shows slight inhibitory activity at 10 μM[1]. JK-P3 (1 and 10 μM; 1 hour) does not significantly inhibit VEGF-A-stimulated endothelial tube formation at 1 µM, but almost completely inhibits the ability of endothelial cells to form into elongated hollow tubes in the presence of VEGF-A at 10 µM[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis
Cell Line:
Primary endothelial cells (treated for 7.5 min with 25 ng/mL VEGF-A)[1]
Concentration:
0.01, 0.1, 1 and 10 μM
Incubation Time:
1 hour
Result:
Almost completely inhibited VEGFR2 Y1175 phosphorylation, also inhibited VEGF-A-stimulated PLCγ1, Akt and ERK1/2 phosphorylation.
Cell Proliferation Assay
Cell Line:
HUVEC[1]
Concentration:
0.01, 0.1, 1 and 10 μM
Incubation Time:
16 hours
Result:
Failed to inhibit endothelial cell proliferation at 0.01~1 μM but elicited a small but significant increase in cell proliferation at certain lower concentrations.
分子量
323.35
Formula
C18H17N3O3
CAS 号
942655-44-9
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Kankanala J, et al. A combinatorial in silico and cellular approach to identify a new class of compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis. Br J Pharmacol. 2012;166(2):737-748.
VEGFR-2-IN-11 (Compound 8h) is a potent VEGFR-2 inhibitor with an IC50 of 60.27 nM. VEGFR-2-IN-11 shows antitumor activity and induces cell apoptosis[1].
IC50 & Target
VEGFR-2
60.27 nM (IC50)
体外研究 (In Vitro)
VEGFR-2-IN-11 (Compound 8h) (0-100 µM) shows antiproliferation activities against tumor cells and induces a low toxic effect in normal cells[1]. VEGFR-2-IN-11 (4.92 µM, 24h) arrests the cell cycle on MCF-7 at a G1/S phase and induces MCF-7 cell apoptosis[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
HCT-116, HEPG-2, and MCF-7
Concentration:
0-100 µM
Incubation Time:
Result:
Showed antiproliferation activities with IC50 values of 8.62 ± 0.7, 10.18 ± 0.8, and 4.92 ± 0.2 µM against HCT-116, HEPG-2, and MCF-7 cells, respectively.
Cell Cycle Analysis[1]
Cell Line:
MCF-7
Concentration:
4.92 µM
Incubation Time:
24 h
Result:
Resulted in a significant increase in the ratio of MCF-7 cells in the G0/G1 phase from 45.81 % (untreated cells) to 49.18 % and the S phase from 39.14% (untreated cells) to 43.22% with a concomitant decrease in the number of cells in G2/M phase by 7.6% compared to untreated control (15.05%).
Apoptosis Analysis[1]
Cell Line:
MCF-7
Concentration:
4.92 µM
Incubation Time:
24 h
Result:
Induced the early apoptosis in MCF-7 (3.46%) 6.4 folds over the untreated cells (0.54%). Enhanced the late apoptotic induction by 20.72% compared to untreated control (0.18%). Induced total apoptosis with 36.24%.
Cell Cytotoxicity Assay[1]
Cell Line:
WI-38
Concentration:
0-100 µM
Incubation Time:
Result:
Induced a low toxic effect with an IC50 value of 44.45 ± 3.2 µM against WI-38 cells.
分子量
552.49
Formula
C29H22BrN5S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Abdelrahman Hamdi, et al. Design, synthesis, antitumor, and VEGFR-2 inhibition activities of novel 4-anilino-2-vinyl-quinazolines: Molecular modeling studies. Bioorg Chem. 2022 May;122:105710.
NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively.
IC50 & Target
VEGFR-2
0.02 μM (IC50)
VEGFR-1
0.38 μM (IC50)
mVEGFR-2
0.23 μM (IC50)
VEGFR-3
0.18 μM (IC50)
PDGFR-β
1.4 μM (IC50)
体外研究 (In Vitro)
The enzymatic kinase assays demonstrate that NVP-ACC789 is an inhibitor of human VEGFR-1, VEGFR-2 (mouse VEGFR-2), VEGFR-3 and PDGFR-β with IC50s of 0.38, 0.02 (0.23), 0.18, 1.4 μM, respectively. In VEGF-treated cultures, addition of the VEGFR-2 inhibitor NVP-ACC789 reduces BME cell number to baseline levels from 1 μM. Likewise, bFGF-induced BME cell proliferation is reduced markedly by NVP-ACC789 from 1 to 10 μM, without however reaching basal levels. NVP-ACC789 is found to be a potent inhibitor of VEGF-induced HUVE cell proliferation with an IC50 of 1.6 nM. NVP-ACC789 also completely inhibits VEGF-induced BME and BAE cell invasion and VEGF-C-induced BAE cell invasion. The inhibition is dose-dependent in both cell types with a maximal effect from 1 μM[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
NVP-ACC789 which is given in daily oral doses for 6 days blocks VEGF-induced angiogenesis in a dose-dependent manner. NVP-ACC789 also inhibits the response to bFGF to some extent, but the dose-response curve is not linear for NVP-ACC789[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
405.29
Formula
C21H17BrN4
CAS 号
300842-64-2
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85.
Kinase Assay [1]
Human VEGFR-2-transfected CHO cells are seeded into 6-well plates and grown to about 80% confluency. NVP-ACC789 is added in serial dilutions and the cells incubated for 2 h at 37°C in medium without fetal calf serum (FCS). VEGF (20 ng/mL) is then added. After a 5-min incubation at 37°C, the cells are washed twice with ice-cold phosphate-buffered saline and lysed. Nuclei are removed by centrifugation for 10 min at 4°C. Protein concentrations of the lysates are determined[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [1]
HUVE cell proliferation is determined. Cells are seeded into 1.5% gelatin-coated 96-well plates (5×103 cells per well) and incubated in endothelial cell growth medium containing 5% fetal calf serum (FCS) for 24 h. The medium is replaced with essential basic medium (1.5% FCS), and the cells are incubated for another 24 h. Essential basic medium is then replaced with fresh medium containing either 50 ng/mL VEGF or 0.5 ng/mL bFGF. NVP-ACC789 is added just before addition of growth factors. The cells are incubated for a further 24 h before adding the BrdU labeling solution. Twenty four hours later, the labeling solution is removed, the cells are fixed, and the incorporated BrdU is visualized with a peroxidase-labeled anti-BrdU antibody and TMB substrate[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Porous Teflon chambers (volume, 0.5 mL) filled with 0.8% w/v agar-containing heparin (20 U/mL) with or without VEGF (2 μg/mL) or bFGF (0.3 μg/mL) are implanted subcutaneously on the dorsal flank of female mice. The mice are treated with NVP-ACC789 (p.o. once daily) or vehicle (5% dimethyl sulfoxide, 1% Tween 80 in water) starting 1 day before implantation of the chamber and continuing for 5 days thereafter. At the end of the treatment period, the mice are killed, and the chambers are removed. The vascularized tissue growing around the chamber is removed carefully and weighed, and the blood content is assessed by measuring hemoglobin levels. The percentage inhibition of the angiogenic response (increase in tissue weight or total blood) is calculated. EC50 values are estimated from the dose response curves (% inhibition versus dose). Each experiment is performed with six animals per dose group and each dose is tested in at least two independent experiments[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85.
Ramucirumab is a human VEGFR-2 antagonist for the treatment of solid tumors[1]. Ramucirumab is a recombinant human immunoglobulin G1 monoclonal antibody that binds to the extracellular binding domain of VEGFR-2 and prevents the binding of VEGFR ligands: VEGF-A, VEGF-C, and VEGF-D[2].
IC50 & Target[1][2]
VEGFR-2
Clinical Trial
分子量
143609.63
Formula
C6374H9864N1692O1996S46
CAS 号
947687-13-0
中文名称
雷莫芦单抗
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Fala L. Cyramza (Ramucirumab) Approved for the Treatment of Advanced Gastric Cancer and Metastatic Non-Small-Cell Lung Cancer. Am Health Drug Benefits. 2015 Mar;8(Spec Feature):49-53.
[2]. Oholendt AL, et al. Ramucirumab: A New Therapy for Advanced Gastric Cancer. J Adv Pract Oncol. 2015 Jan-Feb;6(1):71-5.
TIE-2/VEGFR-2 kinase-IN-1 is used for the synthesis of TIE-2 and/or VEGFR-2 inhibitors, extracted from patent WO2003022852, example 14. TIE-2/VEGFR-2 kinase-IN-1 is used for the study of diseases associated with inappropriate angiogenesis[1].
体外研究 (In Vitro)
Angiopoieten 1 is a ligand for the endotheiium-specific receptor tyrosine kinase, TIE-2 is a novel angiogenic factor[1].Inhibition of TIE-2 is expected to serve to disrupt remodeling and maturation of new vasculature initiated by angiogenesis thereby disrupting the angiogenic process. Inhibition at the kinase domain binding site of VEGFR-2 would block phosphorylation of tyrosine residues and serve to disrupt initiation of angiogenesis.
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
241.25
Formula
C13H11N3O2
CAS 号
453590-24-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 5 mg/mL (20.73 mM; ultrasonic and warming and heat to 80°C)
EG00229 is a neuropilin 1 (NRP1) receptor antagonist. EG00229 selectively inhibits VEGF-A binding to NRP1 b1 domain with an IC50 of 3 μM, but has no effect on VEGFA binding to VEGFR-1 and VEGFR-2[1].
IC50 & Target
IC50: 8 μM (125I-VEGF-A binding to PAE/NRP1); 3 μM (bt-VEGF-A binding to purified NRP1 b1 domain)[1].
体外研究 (In Vitro)
EG00229 (Compound 2; 0-100 μM; 48 hours; A549 cells) treatment causes a significant reduction in cell viability over a 48 hours incubation[1]. EG00229 (Compound 2) demonstrates inhibition of VEGF-A binding to NRP1 and attenuates VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells is also observed in HUVECs[1]. EG00229 (Compound 2) selectively inhibits radiolabeled 125I-VEGF-A binding to porcine aortic endothelial (PAE)/NRP1, but not VEGFR2-expressing cells, with an IC50 of 8 μM. EG00229 also inhibits VEGF-A binding to lung carcinoma A549 and prostate carcinoma DU145 cells, which express NRP1, but not VEGFR1 and VEGFR2, with similar potency. Binding of VEGF-A to human umbilical vein endothelial cells (HUVECs), which express VEGFR2, VEGFR1, and NRP1, is also inhibited by EG00229 with an IC50 of 23 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
A549 cells
Concentration:
0 µM, 10 μM, 30 μM, 100 μM
Incubation Time:
48 hours
Result:
Caused a significant reduction in cell viability.
体内研究 (In Vivo)
EG00229 (0-10 mg/kg; intraperitoneal injection; three times per week; for 4 weeks; NSG mice) treatment substantially reduces tumor growth and visible vascularization[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
6-week old female NOD scid IL2 receptor gamma chain knockout mice (NSG mice) with ECS cells[2]
Dosage:
0 mg/kg, 10 mg/kg
Administration:
Intraperitoneal injection; three times per week; for 4 weeks
Result:
Reduces tumor growth and visible vascularization.
分子量
611.60
Formula
C19H20F3N7O7S3
CAS 号
1210945-69-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Jarvis A, et al. Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction. J Med Chem. 2010 Mar 11;53(5):2215-26.
[2]. Grun D, et al. VEGF-A acts via neuropilin-1 to enhance epidermal cancer stem cell survival and formation of aggressive and highly vascularized tumors. Oncogene. 2016 Aug 18;35(33):4379-87.
N-Desethyl Sunitinib (SU-12662) is a metabolite of sunitinib. Sunitinib is a potent, ATP-competitive VEGFR, PDGFRβ and KIT inhibitor with Ki values of 2, 9, 17, 8 and 4 nM for VEGFR -1, -2, -3, PDGFRβ and KIT, respectively[1].
体外研究 (In Vitro)
Sunitinib also potently inhibits Kit and FLT-3[1]. Sunitinib is a potent ATP-competitive inhibitor of VEGFR2 (Flk1) and PDGFRβ with Ki of 9 nM and 8 nM, respectively, displaying >10-fold higher selectivity for VEGFR2 and PDGFR than FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. Sunitinib inhibits VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibits PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively[2]. Sunitinib inhibits phosphorylation of wild-type FLT3, FLT3-ITD, and FLT3-Asp835 with IC50 of 250 nM, 50 nM, and 30 nM, respectively. Sunitinib inhibits the proliferation of MV4;11 and OC1-AML5 cells with IC50 of 8 nM and 14 nM, respectively, and induces apoptosis in a dose-dependent manner[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Sunitinib (20-80 mg/kg/day) exhibits broad and potent dose-dependent anti-tumor activity against a variety of tumor xenograft models including HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435, consistent with the substantial and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo. Sunitinib (80 mg/kg/day) for 21 days leads to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Second round of treatment with Sunitinib remains efficacious against tumors that are not fully regressed during the first round of treatment. Sunitinib treatment results in significant decrease in tumor MVD, with appr 40% reduction in SF763T glioma tumors. SU11248 treatment results in a complete inhibition of additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size[2]. Sunitinib treatment (20 mg/kg/day) dramatically suppresses the growth subcutaneous MV4;11 (FLT3-ITD) xenografts and prolongs survival in the FLT3-ITD bone marrow engraftment model[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
370.42
Formula
C20H23FN4O2
CAS 号
356068-97-8
中文名称
N-去乙基-舒尼替尼
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 6.25 mg/mL (16.87 mM; ultrasonic and warming and heat to 60°C)
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. Sun L, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor r
[2]. Mendel DB, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Can
[3]. O’Farrell AM, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. Epub 2003 Jan 16.
Kinase Assay [1]
IC50 values for Sunitinib against VEGFR2 (Flk-1) and PDGFRβ are determined using glutathione S-transferase fusion proteins containing the complete cytoplasmic domain of the RTK. Biochemical tyrosine kinase assays to quantitate the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4°C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with the addition of 1-5% (w/v) BSA in PBS. Purified GST-fusion proteins are produced in baculovirus-infected insect cells. GST-VEGFR2 and GST-PDGFRβ are then added to the microtiter wells in 2× concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO4, and 0.02% (w/v) BSA. The final enzyme concentration for GST-VEGFR2 or GST-PDGFRβ is 50 ng/mL. Twenty-five μL of diluted sunitinib are subsequently added to each reaction well to produce a range of inhibitor concentrations appropriate for each enzyme. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl2 so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl2 is 10 mM. The plates are incubated for 5-15 minutes at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1:10,000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO4 and incubated for 1 hour at 37°C. The plates are then washed three times with TBST, followed by the addition of goat antirabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). The plates are incubated for 1 hour at 37°C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2′-azino-di-[3-ethylbenzthiazoline sulfonate] as substrate.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [3]
Cells are starved overnight in medium containing 0.1% FBS prior to addition of Sunitinib and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay or trypan blue cell viability assays. Apoptosis is measured 24 hours after Sunitinib addition by Western blotting to detect cleavage of poly (ADP-ribose) polymerase (PARP) or levels of caspase-3.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Sun L, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor r
[2]. Mendel DB, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Can
[3]. O’Farrell AM, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. Epub 2003 Jan 16.
VEGFR-3-IN-1 is a potent and selective VEGFR3 inhibitor with an IC50 of 110.4 nM. VEGFR-3-IN-1 significantly inhibits proliferation and migration of VEGF-C-induced human dermal lymphatic endothelial cells (HDLEC), MDA-MB-231, and MDA-MB-436 cells by inactivating the VEGFR3 signaling pathway, and also effectively inhibits breast cancer growth[1].
IC50 & Target[1]
VEGFR3
110.4 nM (IC50)
体外研究 (In Vitro)
VEGFR-3-IN-1 (compound 38k) exhibits a significantly higher antiproliferative activity on MDA-MB-231 and MDA-MB-436 cells than 10 (IC50 > 50 μM), with IC50 values of 2.22 and 3.50 μM, respectively[1]. VEGFR-3-IN-1 markedly suppresses the phosphorylation of VEGFR3 and its downstream proteins in a dose-dependent manner[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
MDA-MB-231 and MDA-MB-436 cells
Concentration:
100 nM
Incubation Time:
48 hours
Result:
Exerted antimigration and antiproliferative activities through targeting VEGFR3 in MDA-MB-231 and MDA-MB-436 cells.
Western Blot Analysis[1]
Cell Line:
HDLEC cells
Concentration:
10-500 nM
Incubation Time:
Result:
Antilymphangiogenic activities of VEGFR-3-IN-1 by suppressing the expression of VEGFR3.
体内研究 (In Vivo)
VEGFR-3-IN-1 (50, 25 mg/kg; p.o.) reduces the tumor volume, and displays the strongest inhibitory activity in mice, with a growth inhibition rate of 61.9%[1]. VEGFR-3-IN-1 (10 mg/kg; p.o.) treatment shows the Cmax, AUC0-t , AUC0-∞ and t1/2 values of 420 ng/mL, 9219 ng h/mL, 12304 ng h/mL and 16 hours, respectively[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Nude mice (carrying xenografted BC)[1]
Dosage:
50 mg/kg
Administration:
P.o.;once
Result:
Reduced the tumor volume, and displayed the strongest inhibitory activity in mice.
Animal Model:
Sprague-Dawley (SD) rats [1]
Dosage:
10 mg/kg
Administration:
P.o. (Pharmacokinetic Analysis)
Result:
The Cmax, AUC0-t , AUC0-∞ and t1/2 were 420 ng/mL, 9219 ng h/mL, 12304 ng h/mL and 16 hours, respectively.
分子量
616.10
Formula
C29H29ClF3N7OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Li Y, Yang G, et al. Discovery, Synthesis, and Evaluation of Highly Selective Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Inhibitor for the Potential Treatment of Metastatic Triple-Negative Breast Cancer. J Med Chem. 2021;64(16):12022-12048.
